A method for the detection of digoxin in human plasma has been worked out in our laboratory recently. This analysis depends upon cleanup procedures using thin layer chromatography, derivative formation to provide strong electron affinity by addition of fluorine atoms, and detection by the electron capture detector in the gas liquid chromatograph. This procedure takes about 4-5 hours for 1-5 determinations, and requires close attention and full time surveillance by a technician. Error creeps into the method through contamination from time to time. This is a serious problem because of the small amounts of drug contained in an ordinary plasma sample. Thus, at therapeutic levels of digoxin there are above 10-20 nanograms of drug in 10 ml of plasma. We believe that the method can be made more efficient and at the same time more practicable by using a completely closed system, such as a liquid chromatograph. Preliminary experiments demonstrate the feasibility of trapping the cardiac glycosides on anion exchange columns that have been treated with borate. Elution requires strong acid, and this limits the use of the method because glycosides are hydrolyzed. An alternative method employing organic solvents and higher pressures and liquid-liquid chromatography seems to hold greater promise at the moment, and this is being tested.